Ignite Creation Date:
2025-12-24 @ 6:56 PM
Ignite Modification Date:
2025-12-26 @ 6:11 AM
Study NCT ID:
NCT00276757
Status:
COMPLETED
Last Update Posted:
2014-01-10
First Post:
2006-01-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Combination Chemotherapy in Treating Young Patients With Langerhans Cell Histiocytosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D002955', 'term': 'Leucovorin'}, {'id': 'D008727', 'term': 'Methotrexate'}, {'id': 'D011239', 'term': 'Prednisolone'}, {'id': 'D014747', 'term': 'Vinblastine'}], 'ancestors': [{'id': 'D005575', 'term': 'Formyltetrahydrofolates'}, {'id': 'D013763', 'term': 'Tetrahydrofolates'}, {'id': 'D005492', 'term': 'Folic Acid'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003067', 'term': 'Coenzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}, {'id': 'D000630', 'term': 'Aminopterin'}, {'id': 'D011246', 'term': 'Pregnadienetriols'}, {'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D014748', 'term': 'Vinca Alkaloids'}, {'id': 'D046948', 'term': 'Secologanin Tryptamine Alkaloids'}, {'id': 'D026121', 'term': 'Indole Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D054836', 'term': 'Indolizidines'}, {'id': 'D007212', 'term': 'Indolizines'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'primaryPurpose': 'TREATMENT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 376}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2001-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2007-05', 'completionDateStruct': {'date': '2013-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-01-09', 'studyFirstSubmitDate': '2006-01-12', 'studyFirstSubmitQcDate': '2006-01-12', 'lastUpdatePostDateStruct': {'date': '2014-01-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2006-01-13', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['childhood Langerhans cell histiocytosis'], 'conditions': ['Childhood Langerhans Cell Histiocytosis']}, 'referencesModule': {'references': [{'pmid': '23589673', 'type': 'DERIVED', 'citation': 'Gadner H, Minkov M, Grois N, Potschger U, Thiem E, Arico M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. doi: 10.1182/blood-2012-09-455774. Epub 2013 Apr 15.'}]}, 'descriptionModule': {'briefSummary': 'RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of Langerhans cell histiocytosis, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may be an effective treatment for Langerhans cell histiocytosis.\n\nPURPOSE: This randomized clinical trial is studying combination chemotherapy to see how well it works in treating young patients with Langerhans cell histiocytosis.', 'detailedDescription': 'OBJECTIVES:\n\nPrimary\n\n* Compare the efficacy, in terms of response to initial therapy, of prednisolone, vinblastine, and mercaptopurine with vs without methotrexate and leucovorin calcium in young patients with Langerhans cell histiocytosis.\n* Compare the progression-free survival of patients with low-risk Langerhans cell histiocytosis who responded to initial therapy who are then treated with 6-month vs 12-month continuation therapy comprising prednisolone and vinblastine.\n\nSecondary\n\n* Compare the acute and long-term toxicity and the incidence of permanent effects.\n* Compare the overall and progression-free survival, response rate, and time until response.\n\nOUTLINE: This is a randomized, multicenter study with one pilot nonrandomized stratum. Patients are stratified according to number of systems involved (multiple vs single) and organs involved (at risk vs low risk).\n\n* Stratum 1 (at risk patients): Patients are further stratified according to participating center. Patients are randomized to 1 of 2 treatment arms (arms I and II).\n\n * Arm I:\n\n * Initial therapy: Patients receive oral prednisolone 3 times daily on days 1-28 followed by a taper on days 29-42 and vinblastine IV on days 1, 8, 15, 22, 29, and 36. Patients achieving nonactive disease (NAD) after course 1 proceed to continuation therapy. Patients achieving intermediate response or disease regression receive a second course\\* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.\n * Continuation therapy: Patients receive oral mercaptopurine daily for 3 weeks, pulsed oral prednisolone 3 times daily on days 1-5, and vinblastine IV on day 1. Treatment repeats every 3 weeks until day 365 from the beginning of therapy in the absence of disease progression or unacceptable toxicity.\n * Arm II:\n\n * Initial therapy: Patients receive prednisone and vinblastine as in arm I initial therapy. Patients also receive methotrexate IV over 24 hours on days 1, 15, and 29 and oral leucovorin calcium twice daily on days 2,16, and 30. Patients achieving NAD after course 1 proceed to continuation therapy. Patients achieving intermediate response or disease regression receive a second course\\* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.\n * Continuation therapy: Patients receive oral mercaptopurine daily for 3 weeks, pulsed oral prednisolone 3 times daily on days 1-5, vinblastine IV on day 1, and oral methotrexate on day 1. Treatment repeats every 3 weeks until day 365 from the beginning of therapy in the absence of disease progression or unacceptable toxicity.\n* Stratum 2 (low-risk patients): Patients are stratified according to age at diagnosis (≤ 2 vs \\> 2) and participating center. Patients are randomized to 1 of 2 treatment arms (arms III and IV) after the first course of initial therapy.\n\n * Arm III:\n\n * Initial therapy: Patients receive prednisolone and vinblastine as in course 1 of stratum 1 arm I initial therapy. Patients achieving NAD or disease regression after course 1 proceed to continuation therapy. Patients achieving intermediate or worse response receive a second course\\* of initial therapy. Patients achieving NAD, disease regression, or intermediate response after course 2 proceed to continuation therapy.\n * Continuation therapy: Patients receive prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 182 from the beginning of initial therapy in the absence of disease progression or unacceptable toxicity.\n * Arm IV:\n\n * Initial therapy: Patients receive 1-2 courses of prednisolone and vinblastine as in stratum 2 arm III.\n * Continuation therapy: Patients receive pulsed prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 365 from the beginning of initial therapy in the absence of disease progression or unacceptable toxicity.\n* Stratum 3 (pilot study) (patients with multifocal bone disease and/or special sites):\n\n * Initial therapy: Patients receive prednisolone and vinblastine as in stratum 1 arm I initial therapy. Patients achieving NAD or disease regression after course 1 proceed to continuation therapy. Patients with disease progression receive a second course\\* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.\n * Continuation therapy: Patients receive pulsed prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 182 from the beginning of initial therapy in the absence of disease progression or unacceptable disease.\n\nNOTE: \\*Patients receive oral prednisolone 3 times daily on days 43-45, 50-52, 57-59, 64-66, 71-73, and 78-80 only during the second course of initial therapy.\n\nAfter completion of study treatment, patients are followed periodically for 5 years.\n\nPROJECTED ACCRUAL: A total of 376 patients will be accrued for this study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'DISEASE CHARACTERISTICS:\n\n* Histopathologically confirmed diagnosis of Langerhans cell histiocytosis according to the criteria defined by the Histiocyte Society\n\n * Demonstration of CD1a antigenic determinants on the surface of lesional cells (by immunocytology or immunohistology) or Birbeck granules in lesional cells by electron microscopy\n* Considered at risk or low risk according to the following criteria:\n\n * Multi-system at risk disease, defined as involvement of one or more risk organs (i.e., hematopoietic system, liver, spleen, or lungs)\n\n * No single-system lung involvement\n * Multi-system low-risk disease\n\n * Multiple organs involved but without involvement of risk organs\n * Single-system disease\n\n * Multifocal bone disease (i.e., lesions in 2 or more different bones)\n * Localized special site involvement, such as CNS-risk lesions with intracranial soft tissue extension or vertebral lesions with intraspinal soft tissue extension\n\n * Vault lesions are not regarded as CNS-risk lesions\n\nPATIENT CHARACTERISTICS:\n\n* Not pregnant or nursing\n* Negative pregnancy test\n* Fertile patients must use effective contraception\n\nPRIOR CONCURRENT THERAPY:\n\n* No prior treatment for Langerhans cell histiocytosis'}, 'identificationModule': {'nctId': 'NCT00276757', 'briefTitle': 'Combination Chemotherapy in Treating Young Patients With Langerhans Cell Histiocytosis', 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'Treatment Protocol of the Third International Study For Langerhans Cell Histiocytosis', 'orgStudyIdInfo': {'id': 'CDR0000454768'}, 'secondaryIdInfos': [{'id': 'HISTSOC-LCH-III'}, {'id': 'CCLG-LCH-III'}, {'id': 'EU-20587'}, {'id': 'CCLG-LCH-2002-07'}, {'id': 'UMN-2006NT004'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'leucovorin calcium', 'type': 'DRUG'}, {'name': 'methotrexate', 'type': 'DRUG'}, {'name': 'prednisolone', 'type': 'DRUG'}, {'name': 'vinblastine sulfate', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '55455', 'city': 'Minneapolis', 'state': 'Minnesota', 'country': 'United States', 'facility': 'Masonic Cancer Center at University of Minnesota', 'geoPoint': {'lat': 44.97997, 'lon': -93.26384}}, {'zip': '45229-3039', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '37232-9700', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': "Vanderbilt Children's Hospital", 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '77030-2399', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': "Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital", 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '1245', 'city': 'Buenos Aires', 'state': 'Buenos Aires', 'country': 'Argentina', 'facility': 'Hospital de Pediatria Garrahan'}, {'zip': 'A-1090', 'city': 'Vienna', 'country': 'Austria', 'facility': "St. Anna Children's Hospital", 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': 'M5G 1X8', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Hospital for Sick Children', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '44093', 'city': 'Nantes', 'country': 'France', 'facility': 'CHR Hotel Dieu', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}, {'zip': 'D-20246', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'University Medical Center Hamburg - Eppendorf', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '12', 'city': 'Dublin', 'country': 'Ireland', 'facility': "Our Lady's Hospital for Sick Children Crumlin", 'geoPoint': {'lat': 53.33306, 'lon': -6.24889}}, {'zip': '27100', 'city': 'Pavia', 'country': 'Italy', 'facility': 'Fondazione I.R.C.C.S. Policlinico San Matteo', 'geoPoint': {'lat': 45.19205, 'lon': 9.15917}}, {'zip': 'S-171 76', 'city': 'Stockholm', 'country': 'Sweden', 'facility': 'Karolinska University Hospital - Solna', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}, {'zip': 'B4 6NH', 'city': 'Birmingham', 'state': 'England', 'country': 'United Kingdom', 'facility': "Birmingham Children's Hospital", 'geoPoint': {'lat': 52.48142, 'lon': -1.89983}}, {'zip': 'BS2 8AE', 'city': 'Bristol', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Institute of Child Health at University of Bristol', 'geoPoint': {'lat': 51.45523, 'lon': -2.59665}}, {'zip': 'CB2 2QQ', 'city': 'Cambridge', 'state': 'England', 'country': 'United Kingdom', 'facility': "Addenbrooke's Hospital", 'geoPoint': {'lat': 52.2, 'lon': 0.11667}}, {'zip': 'LS9 7TF', 'city': 'Leeds', 'state': 'England', 'country': 'United Kingdom', 'facility': "Leeds Cancer Centre at St. James's University Hospital", 'geoPoint': {'lat': 53.79648, 'lon': -1.54785}}, {'zip': 'LE1 5WW', 'city': 'Leicester', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Leicester Royal Infirmary', 'geoPoint': {'lat': 52.6386, 'lon': -1.13169}}, {'zip': 'LE1 6TH', 'city': 'Leicester', 'state': 'England', 'country': 'United Kingdom', 'facility': "Children's Cancer and Leukaemia Group", 'geoPoint': {'lat': 52.6386, 'lon': -1.13169}}, {'zip': 'L12 2AP', 'city': 'Liverpool', 'state': 'England', 'country': 'United Kingdom', 'facility': "Royal Liverpool Children's Hospital, Alder Hey", 'geoPoint': {'lat': 53.41058, 'lon': -2.97794}}, {'zip': 'E1 1BB', 'city': 'London', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Royal London Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'zip': 'WC1N 3JH', 'city': 'London', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Great Ormond Street Hospital for Children', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'zip': 'M27 4HA', 'city': 'Manchester', 'state': 'England', 'country': 'United Kingdom', 'facility': "Royal Manchester Children's Hospital", 'geoPoint': {'lat': 53.48095, 'lon': -2.23743}}, {'zip': 'NE1 4LP', 'city': 'Newcastle upon Tyne', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Sir James Spence Institute of Child Health at Royal Victoria Infirmary', 'geoPoint': {'lat': 54.97328, 'lon': -1.61396}}, {'zip': 'NG7 2UH', 'city': 'Nottingham', 'state': 'England', 'country': 'United Kingdom', 'facility': "Queen's Medical Centre", 'geoPoint': {'lat': 52.9536, 'lon': -1.15047}}, {'zip': '0X3 9DU', 'city': 'Oxford', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Oxford Radcliffe Hospital', 'geoPoint': {'lat': 51.75222, 'lon': -1.25596}}, {'zip': 'S10 2TH', 'city': 'Sheffield', 'state': 'England', 'country': 'United Kingdom', 'facility': "Children's Hospital - Sheffield", 'geoPoint': {'lat': 53.38297, 'lon': -1.4659}}, {'zip': 'SO16 6YD', 'city': 'Southampton', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Southampton General Hospital', 'geoPoint': {'lat': 50.90395, 'lon': -1.40428}}, {'zip': 'SM2 5PT', 'city': 'Sutton', 'state': 'England', 'country': 'United Kingdom', 'facility': 'Royal Marsden - Surrey', 'geoPoint': {'lat': 51.35, 'lon': -0.2}}, {'zip': 'BT12 6BE', 'city': 'Belfast', 'state': 'Northern Ireland', 'country': 'United Kingdom', 'facility': 'Royal Belfast Hospital for Sick Children', 'geoPoint': {'lat': 54.59682, 'lon': -5.92541}}, {'zip': 'AB25 2ZG', 'city': 'Aberdeen', 'state': 'Scotland', 'country': 'United Kingdom', 'facility': "Royal Aberdeen Children's Hospital", 'geoPoint': {'lat': 57.14369, 'lon': -2.09814}}, {'zip': 'EH9 1LF', 'city': 'Edinburgh', 'state': 'Scotland', 'country': 'United Kingdom', 'facility': 'Royal Hospital for Sick Children', 'geoPoint': {'lat': 55.95206, 'lon': -3.19648}}, {'zip': 'G3 8SJ', 'city': 'Glasgow', 'state': 'Scotland', 'country': 'United Kingdom', 'facility': 'Royal Hospital for Sick Children', 'geoPoint': {'lat': 55.86515, 'lon': -4.25763}}, {'zip': 'CF14 4XW', 'city': 'Cardiff', 'state': 'Wales', 'country': 'United Kingdom', 'facility': 'Childrens Hospital for Wales', 'geoPoint': {'lat': 51.48, 'lon': -3.18}}], 'overallOfficials': [{'name': 'Kenneth L. McClain, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': "Texas Children's Cancer Center"}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Histiocyte Society', 'class': 'OTHER'}}}}